The effect of different classes of antihypertensive drugs on incident diabetes mellitus is controversial because traditional meta-analyses are hindered by heterogeneity across trials and the absence of trials comparing angiotensin-converting-enzyme (ACE) inhibitors with angiotensin-receptor blockers (ARB). We therefore undertook a network meta-analysis, which accounts for both direct and indirect comparisons to assess the effects of antihypertensive agents on incident diabetes.

Poverty and associated health, nutrition, and social factors prevent at least 200 million children in developing countries from attaining their developmental potential. We review the evidence linking compromised development with modifiable biological and psychosocial risks encountered by children from birth to 5 years of age. We identify four key risk factors where the need for intervention is urgent: stunting, inadequate cognitive stimulation, iodine deficiency, and iron deficiency anaemia. The evidence is also sufficient to warrant interventions for malaria, intrauterine growth restriction, maternal depression, exposure to violence, and exposure to heavy metals. We discuss the research needed to clarify the effect of other potential risk factors on child development. The prevalence of the risk factors and their effect on development and human potential are substantial. Furthermore, risks often occur together or cumulatively, with concomitant increased adverse effects on the development of the world's poorest children.

Regrettably, exposure to trauma is common worldwide, and can have serious adverse psychological results. The introduction of the notion of post-traumatic stress disorder has led to increasing medicalisation of the problem. This awareness has helped popular acceptance of the reality of post-traumatic psychiatric sequelae, which has boosted research into the pathogenesis of the disorder, leading to improved pharmacological and psychological management. The subjective experience of trauma and subsequent expression of symptoms vary considerably over space and time, and we emphasise that not all psychological distress or psychiatric disorders after trauma should be termed post-traumatic stress disorder. There are limits to the medicalisation of distress and there is value in focusing on adaptive coping during and after traumas. Striking a balance between a focus on heroism and resilience versus victimhood and pathological change is a crucial and constant issue after trauma for both clinicians and society. In this Review we discuss the advantages and disadvantages of medicalising trauma response, using examples from South Africa, the Armed Services, and post-disaster, to draw attention to our argument.

Despite three decades of prenatal screening for congenital toxoplasmosis in some European countries, uncertainty remains about the effectiveness of prenatal treatment.

Antiobesity treatment is recommended for selected patients in whom lifestyle modification is unsuccessful. Two antiobesity drugs are currently licensed for long-term use. Orlistat, a gastrointestinal lipase inhibitor, reduces weight by around 3 kg on average and decreases progression to diabetes in high-risk patients; adverse gastrointestinal effects are common. Sibutramine, a monoamine-reuptake inhibitor, results in mean weight losses of 4-5 kg, but is associated with increases in blood pressure and pulse rate. Rimonabant, the first of the endocannabinoid receptor antagonists, reduces weight by 4-5 kg on average and improves waist circumference and concentrations of HDL cholesterol and triglyceride; however, an increased incidence of mood-related disorders has been reported. To date, all antiobesity drug trials have been limited by their high attrition rates and lack of long-term morbidity and mortality data. Other promising antiobesity drugs, including those acting within the central melanocortin pathway, are in development, but are years away from clinical use. In light of the lack of successful weight-loss treatments and the public-health implications of the obesity pandemic, the development of safe and effective drugs should be a priority. However, as new drugs are developed we suggest that the assessment processes should include both surrogate endpoints (ie, weight loss) and clinical outcomes (ie, major obesity-related morbidity and mortality). Only then can patients and their physicians be confident that the putative benefits of such drugs outweigh their risks and costs.

Dental caries, otherwise known as tooth decay, is one of the most prevalent chronic diseases of people worldwide; individuals are susceptible to this disease throughout their lifetime. Dental caries forms through a complex interaction over time between acid-producing bacteria and fermentable carbohydrate, and many host factors including teeth and saliva. The disease develops in both the crowns and roots of teeth, and it can arise in early childhood as an aggressive tooth decay that affects the primary teeth of infants and toddlers. Risk for caries includes physical, biological, environmental, behavioural, and lifestyle-related factors such as high numbers of cariogenic bacteria, inadequate salivary flow, insufficient fluoride exposure, poor oral hygiene, inappropriate methods of feeding infants, and poverty. The approach to primary prevention should be based on common risk factors. Secondary prevention and treatment should focus on management of the caries process over time for individual patients, with a minimally invasive, tissue-preserving approach.

Alcohol abuse and dependence disorders are common in the 10% of hospitalised patients who need admission to the intensive care unit (ICU), but these disorders are often undiagnosed. The systemic effects from the excessive use of alcohol increase susceptibility to, or directly cause various important disorders in the critically ill. Early recognition of alcohol abuse and dependence is necessary and should prompt consideration of several alcohol-specific diagnoses that have important prognostic and therapeutic implications for these patients. We discuss the use of screening tests to improve the identification of alcohol abuse and dependence disorders, the epidemiology and pathogenesis of important alcohol-related disorders, differences in the presentation of several common alcohol-related diagnoses in the ICU, and important alcohol-specific therapies.

Neurodevelopmental disorders such as autism, attention deficit disorder, mental retardation, and cerebral palsy are common, costly, and can cause lifelong disability. Their causes are mostly unknown. A few industrial chemicals (eg, lead, methylmercury, polychlorinated biphenyls [PCBs], arsenic, and toluene) are recognised causes of neurodevelopmental disorders and subclinical brain dysfunction. Exposure to these chemicals during early fetal development can cause brain injury at doses much lower than those affecting adult brain function. Recognition of these risks has led to evidence-based programmes of prevention, such as elimination of lead additives in petrol. Although these prevention campaigns are highly successful, most were initiated only after substantial delays. Another 200 chemicals are known to cause clinical neurotoxic effects in adults. Despite an absence of systematic testing, many additional chemicals have been shown to be neurotoxic in laboratory models. The toxic effects of such chemicals in the developing human brain are not known and they are not regulated to protect children. The two main impediments to prevention of neurodevelopmental deficits of chemical origin are the great gaps in testing chemicals for developmental neurotoxicity and the high level of proof required for regulation. New, precautionary approaches that recognise the unique vulnerability of the developing brain are needed for testing and control of chemicals.

Generalised anxiety disorder is a persistent and common disorder, in which the patient has unfocused worry and anxiety that is not connected to recent stressful events, although it can be aggravated by certain situations. This disorder is twice as common in women than it is in men. Generalised anxiety disorder is characterised by feelings of threat, restlessness, irritability, sleep disturbance, and tension, and symptoms such as palpitations, dry mouth, and sweating. These symptoms are recognised as part of the anxiety syndrome rather than independent complaints. The symptoms overlap greatly with those of other common mental disorders and we could regard the disorder as part of a spectrum of mood and related disorders rather than an independent disorder. Generalised anxiety disorder has a relapsing course, and intervention rarely results in complete resolution of symptoms, but in the short term and medium term, effective treatments include psychological therapies, such as cognitive behavioural therapy; self-help approaches based on cognitive behavioural therapy principles; and pharmacological treatments, mainly selective serotonin reuptake inhibitors.

Public health interventions aimed at children in Mexico have placed the country among the seven countries on track to achieve the goal of child mortality reduction by 2015. We analysed census data, mortality registries, the nominal registry of children, national nutrition surveys, and explored temporal association and biological plausibility to explain the reduction of child, infant, and neonatal mortality rates. During the past 25 years, child mortality rates declined from 64 to 23 per 1000 livebirths. A dramatic decline in diarrhoea mortality rates was recorded. Polio, diphtheria, and measles were eliminated. Nutritional status of children improved significantly for wasting, stunting, and underweight. A selection of highly cost-effective interventions bridging clinics and homes, what we called the diagonal approach, were central to this progress. Although a causal link to the reduction of child mortality was not possible to establish, we saw evidence of temporal association and biological plausibility to the high level of coverage of public health interventions, as well as significant association to the investments in women education, social protection, water, and sanitation. Leadership and continuity of public health policies, along with investments on institutions and human resources strengthening, were also among the reasons for these achievements.

Sexually transmitted infections other than HIV are important global health issues. They have, however, been neglected as a public-health priority and control efforts continue to fail. Sexually transmitted infections, by their nature, affect individuals, who are part of partnerships and larger sexual networks, and in turn populations. We propose a framework of individual, partnership, and population levels for examining the effects of sexually transmitted infections and interventions to control them. At the individual level we have a range of effective diagnostic tests, treatments, and vaccines. These options are unavailable or inaccessible in many resource-poor settings, where syndromic management remains the core intervention for individual case management. At the partnership level, partner notification and antenatal syphilis screening have the potential to prevent infection and re-infection. Interventions delivered to whole populations, or groups in whom the risks of infection and onward transmission are very high, have the greatest potential effect. Improvements to the infrastructure of treatment services can reduce the incidence of syphilis and gonorrhoea or urethritis. Strong evidence for the effectiveness of most other interventions on population-level outcomes is, however, scarce. Effective action requires a multifaceted approach including better basic epidemiological and surveillance data, high quality evidence about effectiveness of individual interventions and programmes, better methods to get effective interventions onto the policy agenda, and better advocacy and more commitment to get them implemented properly. We must not allow stigma, prejudice, and moral opposition to obstruct the goals of infectious disease control.

Severe acute malnutrition (SAM) is defined as a weight-for-height measurement of 70% or less below the median, or three SD or more below the mean National Centre for Health Statistics reference values, the presence of bilateral pitting oedema of nutritional origin, or a mid-upper-arm circumference of less than 110 mm in children age 1-5 years. 13 million children under age 5 years have SAM, and the disorder is associated with 1 million to 2 million preventable child deaths each year. Despite this global importance, child-survival programmes have ignored SAM, and WHO does not recognise the term "acute malnutrition". Inpatient treatment is resource intensive and requires many skilled and motivated staff. Where SAM is common, the number of cases exceeds available inpatient capacity, which limits the effect of treatment; case-fatality rates are 20-30% and coverage is commonly under 10%. Programmes of community-based therapeutic care substantially reduce case-fatality rates and increase coverage rates. These programmes use new, ready-to-use, therapeutic foods and are designed to increase access to services, reduce opportunity costs, encourage early presentation and compliance, and thereby increase coverage and recovery rates. In community-based therapeutic care, all patients with SAM without complications are treated as outpatients. This approach promises to be a successful and cost-effective treatment strategy.

Since 2001, Mexico has been designing, legislating, and implementing a major health-system reform. A key component was the creation of Seguro Popular, which is intended to expand insurance coverage over 7 years to uninsured people, nearly half the total population at the start of 2001. The reform included five actions: legislation of entitlement per family affiliated which, with full implementation, will increase public spending on health by 0.8-1.0% of gross domestic product; creation of explicit benefits packages; allocation of monies to decentralised state ministries of health in proportion to number of families affiliated; division of federal resources flowing to states into separate funds for personal and non-personal health services; and creation of a fund to protect families against catastrophic health expenditures. Using the WHO health-systems framework, we used a wide range of datasets to assess the effect of this reform on different dimensions of the health system. Key findings include: affiliation is preferentially reaching the poor and the marginalised communities; federal non-social security expenditure in real per-head terms increased by 38% from 2000 to 2005; equity of public-health expenditure across states improved; Seguro Popular affiliates used more inpatient and outpatient services than uninsured people; effective coverage of 11 interventions has improved between 2000 and 2005-06; inequalities in effective coverage across states and wealth deciles has decreased over this period; catastrophic expenditures for Seguro Popular affiliates are lower than for uninsured people even though use of services has increased. We present some lessons for Mexico based on this interim evaluation and explore implications for other countries considering health reforms.

Ending the silent pandemic of unsafe abortion is an urgent public-health and human-rights imperative. As with other more visible global-health issues, this scourge threatens women throughout the developing world. Every year, about 19-20 million abortions are done by individuals without the requisite skills, or in environments below minimum medical standards, or both. Nearly all unsafe abortions (97%) are in developing countries. An estimated 68 000 women die as a result, and millions more have complications, many permanent. Important causes of death include haemorrhage, infection, and poisoning. Legalisation of abortion on request is a necessary but insufficient step toward improving women's health; in some countries, such as India, where abortion has been legal for decades, access to competent care remains restricted because of other barriers. Access to safe abortion improves women's health, and vice versa, as documented in Romania during the regime of President Nicolae Ceausescu. The availability of modern contraception can reduce but never eliminate the need for abortion. Direct costs of treating abortion complications burden impoverished health care systems, and indirect costs also drain struggling economies. The development of manual vacuum aspiration to empty the uterus, and the use of misoprostol, an oxytocic agent, have improved the care of women. Access to safe, legal abortion is a fundamental right of women, irrespective of where they live. The underlying causes of morbidity and mortality from unsafe abortion today are not blood loss and infection but, rather, apathy and disdain toward women.

Acute myeloid leukaemia (AML) is a heterogeneous clonal disorder of haemopoietic progenitor cells and the most common malignant myeloid disorder in adults. The median age at presentation for patients with AML is 70 years. In the past few years, research in molecular biology has been instrumental in deciphering the pathogenesis of the disease. Genetic defects are thought to be the most important factors in determining the response to chemotherapy and outcome. Whereas significant progress has been made in the treatment of younger adults, the prospects for elderly patients have remained dismal, with median survival times of only a few months. This difference is related to comorbidities associated with ageing and to disease biology. Current efforts in clinical research focus on the assessment of targeted therapies. Such new approaches will probably lead to an increase in the cure rate.

Absence of financial protection in health is a recently diagnosed "disease" of health systems. The most obvious symptom is that families face economic ruin and poverty as a consequence of financing their health care. Mexico was one of the first countries to diagnose the problem, attribute it to lack of financial protection, and propose systemic therapy through health reform. In this article we assess how Mexico turned evidence on catastrophic and impoverishing health spending into a catalyst for institutional renovation through the reform that created Seguro Popular (Popular Health Insurance). We present 15-year trends on the evolution of catastrophic and impoverishing health spending, including evidence on how the situation is improving. The results of the Mexican experience suggest an important role for the organisation and financing of the health system in reducing impoverishment and protecting households during periods of individual and collective financial crisis.

Promotion of family planning in countries with high birth rates has the potential to reduce poverty and hunger and avert 32% of all maternal deaths and nearly 10% of childhood deaths. It would also contribute substantially to women's empowerment, achievement of universal primary schooling, and long-term environmental sustainability. In the past 40 years, family-planning programmes have played a major part in raising the prevalence of contraceptive practice from less than 10% to 60% and reducing fertility in developing countries from six to about three births per woman. However, in half the 75 larger low-income and lower-middle income countries (mainly in Africa), contraceptive practice remains low and fertility, population growth, and unmet need for family planning are high. The cross-cutting contribution to the achievement of the Millennium Development Goals makes greater investment in family planning in these countries compelling. Despite the size of this unfinished agenda, international funding and promotion of family planning has waned in the past decade. A revitalisation of the agenda is urgently needed. Historically, the USA has taken the lead but other governments or agencies are now needed as champions. Based on the sizeable experience of past decades, the key features of effective programmes are clearly established. Most governments of poor countries already have appropriate population and family-planning policies but are receiving too little international encouragement and funding to implement them with vigour. What is currently missing is political willingness to incorporate family planning into the development arena.

Hereditary degenerations of the human retina are genetically heterogeneous, with well over 100 genes implicated so far. This Seminar focuses on the subset of diseases called retinitis pigmentosa, in which patients typically lose night vision in adolescence, side vision in young adulthood, and central vision in later life because of progressive loss of rod and cone photoreceptor cells. Measures of retinal function, such as the electroretinogram, show that photoreceptor function is diminished generally many years before symptomic night blindness, visual-field scotomas, or decreased visual acuity arise. More than 45 genes for retinitis pigmentosa have been identified. These genes account for only about 60% of all patients; the remainder have defects in as yet unidentified genes. Findings of controlled trials indicate that nutritional interventions, including vitamin A palmitate and omega-3-rich fish, slow progression of disease in many patients. Imminent treatments for retinitis pigmentosa are greatly anticipated, especially for genetically defined subsets of patients, because of newly identified genes, growing knowledge of affected biochemical pathways, and development of animal models.